Molecular hepatic carcinogenesis: impact of inflammation

Hepatocellular cancer (HCC) represents one of the most rapidly spreading cancers in the world. Most HCC develops in cirrhotic livers after prolonged inflammation, supporting the hypothesis that inflammation contributes to cancer development. Increasing evidence suggests that inflammatory cell recruitment and activation is an important contributor to promoting cancerous malformation in hepatocytes. Intracellular signaling pathways involved in classical inflammatory pathway activation can be altered in parenchymal cells, hepatocytes, in the liver to promote HCC development. Inflammation is triggered by pathogen-derived or endogenous danger-associated molecular patterns via pattern recognition receptors. Activation of the pattern recognition receptors triggers downstream signaling cascades to induce proinflammatory cytokine production, release of reactive oxygen species and modulate cellular responses. Many of these inflammatory mediators have adverse effects on DNA repair and induce DNA methylation, both of which are important elements in HCC development. This review summarizes the key points and discusses recent findings related to the role of inflammation in cancer and HCC development.